This application proposes that basement membrane components of the seminiferous tubules play a determining role in Sertoli cell function and in the formation of a tubular lumen by a selective process of programmed cell death. To examine these possibilities, three approaches will be taken. In Specific Aim 1, an in vitro seminiferous cord model using basement membrane components as a culture substrate will be used. In Specific Aim 2, studies will be focused on the mechanism of signal transduction that occurs after basement membrane components bind to integrins on the surface of Sertoli cells. A major emphasis will be the role of Ca 2+ as a second messenger and protooncogene c-fos as a potential third messenger in Sertoli cell responses to the basement membrane. In Specific Aim 3, the role of the basement membrane as a survival factor for Sertoli cells will be studied, in particular the role and mechanism of seminiferous tubular lumen formation related to Sertoli cell differentiation and its possible programmed cell death.